'Anergic' T cells modulate the T-cell activating capacity of antigen-presenting cells.

Nowadays there is compelling evidence for immunoregulation by T cells. Recently, we showed that so-called 'anergic' T cells are not functionally inert but can act as regulatory cells by actively suppressing other T cell responses. We now show that 'anergic' T cells mediate this suppressive effect via modulation of the T-cell activating capacity of the antigen-presenting cell (APC). Upon removal of the 'anergic' T cells, the suppressive APC phenotype persisted, indicating that 'anergic' T cells conditioned the APC to become a mediator of T cell suppression. The inhibitory signal delivered by 'anergic' T cells depended on the presence of the cognate ligand for the 'anergic' T cell, and appeared to be dominant since previously activated APC were rendered inhibitory as well. These findings imply that APC upon cross-talk with T cells can adopt distinct functional phenotypes ranging from T-cell stimulatory to T-cell suppressive. The contribution of 'anergic' T cells to the functional tuning of APC offers an explanation for the maintenance of 'anergic' T cells in the repertoire, and for their role in immunoregulation.

Growth hormone induces insulin-like growth factor-I gene transcription by a synergistic action of STAT5 and HNF-1alpha.

Salmon insulin-like growth factor-I (sIGF-I) expression is, as in mammals, induced by growth hormone (GH). To elucidate the mechanism by which GH stimulates the transcription of the IGF-I gene, we transiently transfected Hep3B cells expressing the rat GH receptor with a sIGF-I promoter-luciferase reporter construct. Activation of the construct by GH added to the medium of the transfected cells was observed when two specific transcription factors, STAT5 and HNF-1alpha, were simultaneously overexpressed in these cells. This finding demonstrates for the first time a GH-dependent activation of an IGF-I promoter construct in an immortalized laboratory cell line.